Lillehei Heart Institute, University of Minnesota, Minneapolis, MN 55455, USA; Department of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA.
Lillehei Heart Institute, University of Minnesota, Minneapolis, MN 55455, USA; Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USA.
Cell Stem Cell. 2018 Jul 5;23(1):74-85.e6. doi: 10.1016/j.stem.2018.06.010.
Derivation of functional skeletal muscle stem cells from pluripotent cells without genetic modification has proven elusive. Here we show that teratomas formed in adult skeletal muscle differentiate in vivo to produce large numbers of α7-Integrin+ VCAM-1+ myogenic progenitors. When FACS-purified and transplanted into diseased muscles, mouse teratoma-derived myogenic progenitors demonstrate very high engraftment potential. As few as 40,000 cells can reconstitute ∼80% of the tibialis anterior muscle volume. Newly generated fibers are innervated, express adult myosins, and ameliorate dystrophy-related force deficit and fatigability. Teratoma-derived myogenic progenitors also contribute quiescent PAX7+ muscle stem cells, enabling long-term maintenance of regenerated muscle and allowing muscle regeneration in response to subsequent injuries. Transcriptional profiling reveals that teratoma-derived myogenic progenitors undergo embryonic-to-adult maturation when they contribute to the stem cell compartment of regenerated muscle. Thus, teratomas are a rich and accessible source of potent transplantable skeletal muscle stem cells. VIDEO ABSTRACT.
从多能细胞中衍生出具有功能性的骨骼肌干细胞而不进行基因修饰，这一直难以实现。在这里，我们证明了在成年骨骼肌中形成的畸胎瘤在体内分化为大量α7-整合素+VCAM-1+ 成肌祖细胞。当通过 FACS 纯化并移植到患病肌肉中时，来自小鼠畸胎瘤的成肌祖细胞显示出非常高的植入潜力。仅 40,000 个细胞就可以重建约 80%的比目鱼肌体积。新生成的纤维被神经支配，表达成人肌球蛋白，并改善与肌肉萎缩症相关的力量缺陷和疲劳性。畸胎瘤衍生的成肌祖细胞还为静止的 PAX7+ 肌肉干细胞做出贡献，从而能够长期维持再生肌肉，并允许肌肉对随后的损伤做出再生反应。转录谱分析表明，当畸胎瘤衍生的成肌祖细胞为再生肌肉的干细胞区室做出贡献时，它们会经历从胚胎到成年的成熟过程。因此，畸胎瘤是一种丰富且易于获取的具有潜力的可移植骨骼肌干细胞来源。视频摘要。
